The objectives and long-range goals as set out in this application are: (a) to undertake a comprehensive comparative study of the non-protein free amino acids of the various physiological fluids and tissues of the mouse, in order to establish normal values of reference for cancer studies, and (b) to study the changes which take place in such amino acids during neoplastic growth and under various specific therapeutic treatments, to provide greater insight into the mechanisms involved in the control of tissue maintenance and growth. To accomplish these objectives, we propose to systematically analyze the plasma, urine, and various tissues and organs of the mouse for free and for non-protein bound amino acids. These profiles and basic reference values will then be used to compare with results obtained in cancer studies. The plasma studies and preliminary tissue studies with EARAD-1 leukemia/lymphoma will be extended, as will also our preliminary studies on pigmented and non-pigmented melanoma tissues. We will attempt to interpret meaningful variations, as compared with normal mice, in terms of improving our understanding of malignant growth. Where significant variations or differences are found which might be exploitable, experimental therapeutic studies will be initiated. These would include the control of dietary amino acids, the use of specific amino acid antagonists, and the use of specific amino acid-destroying enzymes.